Our initial project was to test the hypothesis that the increased cell proliferation and glycogen in the psoriatic lesional epidermis was due to combination of a low cyclic AMP and a high cyclic GMP. Measurements of cyclic AMP levels in micro-dissected (frozen-dried) epidermis from the psoriatic and healthy skin of the same patient revealed that the level was slightly higher (not lower) in psoriatic epidermis than in uninvolved epidermis; thus the above data do not support the hypothesis. In search of alternative veritable biochemical abnormality we tested the various hormonal sensitivities of skin. When epidermal slices were incubated with hormones and chemicals for activation of cyclic AMP levels in epidermis, 1) epinephrine increased the level markedly in the uninvolved, but not in the lesional psoriatic skin, 2) the response to histamine was reversed, i.e., the presence by the involved skin was much greater than that by the uninvolved and, 3) the response to adenosine was approximately equal. Our data precludes the possibility that the unresponsiveness to epinephrine can be due to a generalized inability of the epidermal psoriatic plaque cell to make a functioning cell membrane. Since we observed no significant change in basic kinetics of cyclic nucleotide phosphodiesterase between the involved and uninvolved skin of psoriasis, these abnormalities of the hormone receptor systems in the lesional epidermis may be significant biochemical factors in rapidly growing epidermal cells (if not specific for psoriasis).